Ubiquinone is a quinone compound widely distributed over living matters, which is also named a benzoquinone derivative (CoQn), e.g. 2,3-dimethoxy-5-methyl-6-polyprenyl-1,4-benzoquinone, known as coenzyme Q (CoQ). Among ubiquinones, ubidecarenone (CoQ10), which exists in higher animals including humans, is known to have a coenzyme activity as well as a vitamin-like activity to improve the efficiency of oxygen utilization. For this reason, it is thought that a composition comprising ubidecarenone acts on a congested tissue, stabilizes bio-membranes and is effective in antioxidation. The pharmacological effects of ubidecarenone have been clinically accepted for alleviating the symptoms of angina, heart failure, ischemic heart disease, and muscular dystrophy. It has also been reported that ubidecarenone is useful as a curative medicine of the congestive mental disorder (minor or intermediate level) under basic therapy and effective against essential hypertension and gum disease, and effective in preventing side-effects of anticancer drugs and psychotropic drugs, etc.
However, almost all the ubiquinones including ubidecarenone are a lipophilic and fat-soluble solid material with low melting points. It is well known that the absorptivity of ubiquinone by oral administration is low due to its low solubility in water. Ubiquinone is absorbed like fat-soluble vitamins to the living body mainly from lymph vessel. Since the amount to be absorbed is very limited, the bioavailability of ubiquinone is low.
Many attempts have been made to improve the bioabsorptivity and the stability of fat-soluble compositions that are hardly soluble in water. They are dissolved in pharmaceutically acceptable solvents such as vegetable oils, e.g. sesame oil, peanut oil, olive oil, soybean oil, cottonseed oil and corn oil, or in animal oils, e.g. fish liver oil, or dispersed and emulsified in an aqueous liquid with various additives such as an emulsifier, a dispersing agent or a surfactant.
Ubidecarenone compositions were also dissolved in a lipophilic solvent such as vegetable oils or animal oils for oral administration, but satisfactory bioabsorptivity has not been attained. U.S. Pat. No. 4,540,602 discloses dissolving ubidecarenone in a lipophilic solvent and emulsifying it in the presence of a water-soluble material. However the technology is not desirable in that the solvent remains in the final composition and, thus, is not acceptable in view of environmental hygiene or regulation of food additives.
There have been reported methods for promoting the absorption of scarcely soluble drugs containing ubidecarenone from lymph vessel, thereby improving its bioavailability. The scarcely soluble drugs containing ubidecarenone were emulsified with polyglycerol unsaturated fatty acid esters (U.S. Pat. No. 4,751,241), and further with a water-soluble material (JP-A 59-51214). However, a polyglycerol unsaturated fatty acid ester is a high-viscosity liquid substance and, therefore, the amount of the polyglycerol unsaturated fatty acid ester to be added is restricted inevitably, and, as a result, the content of ubidecarenone in the composition is restricted. If the content of ubidecarenone in the composition is low, one time dose or the number of daily administration may increase, which will result in lowered medical compliance and lowered QOL (Quality of Life) of a patient. Thus, it is not desirable. Furthermore, it will be difficult for a patient with lowered deglutition to take an increased dosage of the drug.
European Patent 0522433 discloses administering ubidecarenone emulsified with hydrophilic surfactants such as salt of bile acid, Polysorbate 80, and polyoxyethylene hardened castor oil in order to increase the bioavailability of ubidecarenone. However, use of these hydrophilic surfactants in a large amount may happen to trigger disorders of tunica mucosa ventriculi and alimentary canal membrane such as hemolysis, membrane stimulus and membrane deficit, or hypersensitivity. Therefore, the use of such hydrophilic surfactants is not recommendable.
Moreover, since the melting point of ubidecarenone is as low as 50° C. or so, ubidecarenone may sometimes be dissolved in a solid composition such as powders and tablets, causing colored spots by capillarity or oozing out, which may reduce commercial value of the product.